Bacteriophage Therapy: Potential and Problems

Abstract

The antibiotic resistance crisis calls for alternative antimicrobials. Phage therapy (PT) is a registered medicine in Russia. Evidence for its efficacy from controlled clinical tests is currently limited to a large trial of Shigella dysentery prevention and a small treatment trial of Pseudomonas-associated otitis externa trial. A treatment trial of Escherichia coli childhood diarrhea with T4-like phages or a commercial Russian phage cocktail did not show better results than standard treatment. The analysis of this trial and of the multicentre Phagoburn trial revealed problems of PT mainly linked to the fact that PT requires knowledge on the infecting pathogen. A personalized medicine approach with a magistral phage preparation might address both the specificity and regulatory requirements of PT. More preclinical research into pharmaceutical formulation strategies for PT, the identification of phages with broader host range and phages infecting pathogens growing in biofilms is needed. PT is complicated by phage-resistance development and interaction with the immune system and concomitantly given antibiotics, but synergistic interaction are also possible. PT progress depends on standardized preclinical tests probing in vivo relevant phage phenotypes and an evaluation of case studies identifying suitable target infections.